Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

OBJECTIVE To evaluate the impact of environmental factors in Tianmen on clinical indicators of pediatric snoring with allergic rhinitis and to analyze their correlations.This study aims to deepen the understanding of the relationship between environmental factors and pediatric respiratory diseases,and to provide scientific evidence for future prevention and treatment strategies.METHODS A retrospective study was conducted based on the clinical data of 3 071 pediatric patients with snoring admitted to Tianmen First People's Hospital from January 1,2021,to December 31,2023.The 95th percentile values of PM2.5,SO?,NO?,PM10,and CO,as well as the 90th percentile value of O?,in Tianmen during the same period were collected.Correlation analysis and binary logistic regression were used to investigate the association between environmental factors and pediatric snoring with allergic rhinitis.RESULTS Pearson correlation analysis revealed positive correlations among SO?,NO?,PM10,PM2.5,and CO,with the strongest correlation between PM2.5 and PM10(r=0.862,P<0.001).In contrast,O? was negatively correlated with other pollutants,with the most significant negative correlation observed between CO and O?(r=-0.505,P<0.001).Seasonal distribution showed that pollutant levels were significantly lower in summer than in winter.Among the 3 071 patients,840 cases were complicated with allergic rhinitis.Significant differences were observed between the allergic rhinitis and non-allergic rhinitis groups in terms of PM2.5 levels,length of hospital stay,total cost,drug cost,antibiotic cost,year of treatment,and treatment modalities(P<0.05).Logistic regression indicated that PM2.5 was an independent risk factor for pediatric snoring with allergic rhinitis(OR=1.013,95%CI:1.010-1.017,P<0.05),and this remained significant after adjusting for multiple clinical variables(OR=1.010,95%CI:1.007-1.014,P<0.05).ROC curve analysis showed that the combined diagnostic model using PM2.5 and total cost had the highest diagnostic performance(AUC=0.642,95%CI:0.620-0.664),which was superior to PM2.5 alone(AUC=0.636)or total cost alone(AUC=0.623).CONCLUSION Pediatric snoring with allergic rhinitis is closely related to environmental factors,especially PM2.5,which has a significant impact.These findings may provide a scientific basis for targeted environmental interventions and treatment strategies to improve the quality of life in affected children.

Glioma is the most common primary malignant brain tumor and its microenvironment exhibits immunosuppressive properties. Macrophages and T cells are the main immune cells of glioma, which engage in highly dynamic interactions. Cytokines such as interleukin-2 (IL-12), interleukin-10 (IL-10), interferon-γ (IFN-γ),and transforming growth factor-β (TGF-β) determine the direction and intensity of the anti-tumor immune response through finely regulating macrophage polarization and T cell subset differentiation. Co-stimulatory molecules on the surface of T cells are mostly members of the immunoglobulin superfamily (IgSF); in addition,co-stimulatory molecules including CD80/CD86, T cell inducible co-stimulatory molecule and its ligand (ICOS /ICOS-L),CD40L/CD40, OX40L/OX40 and glucocorticoid-induced tumor necrosis factor receptor related protein and its ligand (GITR /GITR-L) are involved in initiating,enhancing or inhibiting T cell activation,and collaboratively shape the overall tumor immune microenvironment. The in-depth understanding of these factors and molecular pathways can help optimize immunotherapeutic strategies for glioma and provide new therapeutic targets.

Abdominal aortic aneurysm(AAA)is a degenerative vascular disease occurring in the lower segment of the aortic diaphragm,mainly manifested by irreversible dilatation of the entire artery,preferably in the elderly population.The pathogenesis of AAA is complex and involves multiple factors,with genetic variations and immune imbalances playing important roles.Its pathological changes mainly include inflammatory cell infiltration,degradation of stromal elastin,and smooth muscle cell death.Rupture of AAA is the most dangerous complication,with a high mortality.Surgery remains the only effective intervention,but carries certain risks and postoperative complications.Early intervention for small abdominal aortic aneurysms to slow down aneurysm expansion and achieve long-term survival is currently a focus of drug and technology research.This article reviews the pathogenesis of AAA and its intervention strategies,and summarizes the research on existing drugs and the use of new targets and technologies,so as to provide insights for better understanding and treatment of AAA.

Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective:To investigate the application effect of propofol combined with remifentanil for anesthesia in children undergoing plasma adenoidectomy.Methods:Clinical data of 103 children who underwent plasma adenoidectomy in our hospital from Apr 2023 to Apr 2024 were retrospectively analyzed.Children were divided into two groups according to different anesthesia schemes.Children who received propofol+ketamine anesthesia were enrolled in the control group(n=52)and children who received propofol+remifentanil anesthesia were enrolled in the study group(n=51).Hemodynamic parameters were compared between the two groups at four time points:before anesthesia(T0),immediately after extubation(T1),5 minutes after extubation(T2),and 10 minutes after extubation(T3).The pain scores(CHIPPS)of the two groups were compared at 10,20,and 30 min after extubation.Post-anesthesia evaluation of discomfort(PAED)and incidence of restlessness during recovery in children were compared.The indicators of stress response(cortisol and epinephrine)were measured preoperatively and 1 day postoperatively.Total perioperative adverse events were analyzed.Results:The recovery times for spontaneous breathing,eye-opening,and extubation in the study group were shorter than those in the control group(P＜0.05).The heart rate and mean arterial pressure level in the study group at T1-T3 were lower than those in the control group(P＜0.05).The CHIPPS scores at 10,20,and 30 min after extubation and PAED scores during the recovery period in the study group were lower than those in the control group(P＜0.05).The incidence of restlessness during the recovery period in the study group was lower than that in the control group(P＜0.05).The levels of cortisol and epinephrine in the study group were lower than those in the control group on day 1 after surgery(P＜0.05).There was no significant difference in the overall incidence of adverse reactions between the two groups(P＞0.05).Conclusion:The use of propofol combined with remifentanil in plasma adenoidectomy can effectively shorten the recovery time of anesthesia in children,enhance analgesic effects,reduce blood circulation fluctuations and stress reactions,and reduce the incidence of restlessness,with reliable safety.

Glioma is the most common primary malignant brain tumor and its microenvironment exhibits immunosuppressive properties. Macrophages and T cells are the main immune cells of glioma, which engage in highly dynamic interactions. Cytokines such as interleukin-2 (IL-12), interleukin-10 (IL-10), interferon-γ (IFN-γ),and transforming growth factor-β (TGF-β) determine the direction and intensity of the anti-tumor immune response through finely regulating macrophage polarization and T cell subset differentiation. Co-stimulatory molecules on the surface of T cells are mostly members of the immunoglobulin superfamily (IgSF); in addition,co-stimulatory molecules including CD80/CD86, T cell inducible co-stimulatory molecule and its ligand (ICOS /ICOS-L),CD40L/CD40, OX40L/OX40 and glucocorticoid-induced tumor necrosis factor receptor related protein and its ligand (GITR /GITR-L) are involved in initiating,enhancing or inhibiting T cell activation,and collaboratively shape the overall tumor immune microenvironment. The in-depth understanding of these factors and molecular pathways can help optimize immunotherapeutic strategies for glioma and provide new therapeutic targets.

Objective:To investigate the application effect of propofol combined with remifentanil for anesthesia in children undergoing plasma adenoidectomy.Methods:Clinical data of 103 children who underwent plasma adenoidectomy in our hospital from Apr 2023 to Apr 2024 were retrospectively analyzed.Children were divided into two groups according to different anesthesia schemes.Children who received propofol+ketamine anesthesia were enrolled in the control group(n=52)and children who received propofol+remifentanil anesthesia were enrolled in the study group(n=51).Hemodynamic parameters were compared between the two groups at four time points:before anesthesia(T0),immediately after extubation(T1),5 minutes after extubation(T2),and 10 minutes after extubation(T3).The pain scores(CHIPPS)of the two groups were compared at 10,20,and 30 min after extubation.Post-anesthesia evaluation of discomfort(PAED)and incidence of restlessness during recovery in children were compared.The indicators of stress response(cortisol and epinephrine)were measured preoperatively and 1 day postoperatively.Total perioperative adverse events were analyzed.Results:The recovery times for spontaneous breathing,eye-opening,and extubation in the study group were shorter than those in the control group(P＜0.05).The heart rate and mean arterial pressure level in the study group at T1-T3 were lower than those in the control group(P＜0.05).The CHIPPS scores at 10,20,and 30 min after extubation and PAED scores during the recovery period in the study group were lower than those in the control group(P＜0.05).The incidence of restlessness during the recovery period in the study group was lower than that in the control group(P＜0.05).The levels of cortisol and epinephrine in the study group were lower than those in the control group on day 1 after surgery(P＜0.05).There was no significant difference in the overall incidence of adverse reactions between the two groups(P＞0.05).Conclusion:The use of propofol combined with remifentanil in plasma adenoidectomy can effectively shorten the recovery time of anesthesia in children,enhance analgesic effects,reduce blood circulation fluctuations and stress reactions,and reduce the incidence of restlessness,with reliable safety.

Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.